pseudo-outbreak due to laboratory cross-contamination: A molecular epidemiology outbreak investigation.

Background: Mycobacterial culture is routinely performed to diagnose tuberculosis (TB) in Canada. Globally, meta-analyses suggest that up to 2% of positive cultures are falsely positive for due to laboratory cross-contamination. Five patients from distinct clinical institutions in Montréal were diagnosed with culture-positive TB as their clinical samples were processed in a centralized mycobacteria laboratory.

Concordance of targeted and whole genome sequencing for Mycobacterium tuberculosis genotypic drug susceptibility testing.

Targeted Next Generation Sequencing (tNGS) and Whole Genome Sequencing (WGS) are increasingly used for genotypic drug susceptibility testing (gDST) of Mycobacterium tuberculosis. Thirty-two multi-drugs resistant and 40 drug susceptible isolates from Madagascar were tested with Deeplex® Myc-TB and WGS using the Mykrobe analysis pipeline. Sixty-four of 72 (89 %) yielded concordant categorical gDST results for drugs tested by both assays.

On-demand, hospital-based, severe acute respiratory coronavirus virus 2 (SARS-CoV-2) genomic epidemiology to support nosocomial outbreak investigations: A prospective molecular epidemiology study.

Objectives: We evaluated the added value of infection control-guided, on demand, and locally performed severe acute respiratory coronavirus virus 2 (SARS-CoV-2) genomic sequencing to support outbreak investigation and control in acute-care settings.

Design And Setting: This 18-month prospective molecular epidemiology study was conducted at a tertiary-care hospital in Montreal, Canada. When nosocomial transmission was suspected by local infection control, viral genomic sequencing was performed locally for all putative outbreak cases.

Integrated immunovirological profiling validates plasma SARS-CoV-2 RNA as an early predictor of COVID-19 mortality.

Despite advances in COVID-19 management, identifying patients evolving toward death remains challenging. To identify early predictors of mortality within 60 days of symptom onset (DSO), we performed immunovirological assessments on plasma from 279 individuals. On samples collected at DSO11 in a discovery cohort, high severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA (vRNA), low receptor binding domain–specific immunoglobulin G and antibody-dependent cellular cytotoxicity, and elevated cytokines and tissue injury markers were strongly associated with mortality, including in patients on mechanical ventilation.

Impact of cobas PCR Media freezing on SARS-CoV-2 viral RNA integrity and whole genome sequencing analyses.

SARS-CoV-2 whole genome sequencing is a molecular biology tool performed to support many aspects of the response to the pandemic. Freezing of primary clinical nasopharyngeal swabs and shipment to reference laboratories is usually required for sequencing. Cobas PCR Media transport medium facilitates high throughput SARS-CoV-2 RT-PCR analyses on cobas platforms.

Ligand-dependent kinase activity of MERTK drives efferocytosis in human iPSC-derived macrophages.

Removal of apoptotic cells by phagocytes (also called efferocytosis) is a crucial process for tissue homeostasis. Professional phagocytes express a plethora of surface receptors enabling them to sense and engulf apoptotic cells, thus avoiding persistence of dead cells and cellular debris and their consequent effects. Dysregulation of efferocytosis is thought to lead to secondary necrosis and associated inflammation and immune activation.

A novel orally available small molecule that inhibits hepatitis B virus expression.

Background & Aims: The hallmarks of chronic HBV infection are a high viral load (HBV DNA) and even higher levels (>100-fold in excess of virions) of non-infectious membranous particles containing the tolerogenic viral S antigen (HBsAg). Currently, standard treatment effectively reduces viremia but only rarely results in a functional cure (defined as sustained HBsAg loss). There is an urgent need to identify novel therapies that reduce HBsAg levels and restore virus-specific immune responsiveness in patients.

Mannoside Glycolipid Conjugates Display Anti-inflammatory Activity by Inhibition of Toll-like Receptor-4 Mediated Cell Activation.

Inhibition of excessive Toll-like receptor 4 (TLR4) signaling is a therapeutic approach pursued for many inflammatory diseases. We report that Mannoside Glycolipid Conjugates (MGCs) selectively blocked TLR4-mediated activation of human monocytes and monocyte-derived dendritic cells (DCs) by lipopolysaccharide (LPS). They potently suppressed pro-inflammatory cytokine secretion and maturation of DCs exposed to LPS, leading to impaired T cell stimulation.

Inhibition of insulin and T3-induced fatty acid synthase by hexanoate.

Fatty acid synthase (FAS) is responsible for the de novo synthesis of palmitate and stearate. This enzyme is activated by insulin and T(3), and inhibited by fatty acids. In this study, we show that insulin and T(3) have an inducing effect on FAS enzymatic activity, which is synergetic when both hormones are present.